1luv: Difference between revisions

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[[Image:1luv.jpg|left|200px]]


{{Structure
==CATALYTIC AND STRUCTURAL EFFECTS OF AMINO-ACID SUBSTITUTION AT HIS 30 IN HUMAN MANGANESE SUPEROXIDE DISMUTASE: INSERTION OF VAL CGAMMA INTO THE SUBSTRATE ACCESS CHANNEL==
|PDB= 1luv |SIZE=350|CAPTION= <scene name='initialview01'>1luv</scene>, resolution 1.85&Aring;
<StructureSection load='1luv' size='340' side='right'caption='[[1luv]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND= <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>
<table><tr><td colspan='2'>[[1luv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LUV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LUV FirstGlance]. <br>
|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Superoxide_dismutase Superoxide dismutase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.15.1.1 1.15.1.1] </span>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.85&#8491;</td></tr>
|GENE=  
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr>
|DOMAIN=
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1luv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1luv OCA], [https://pdbe.org/1luv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1luv RCSB], [https://www.ebi.ac.uk/pdbsum/1luv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1luv ProSAT]</span></td></tr>
|RELATEDENTRY=[[1abm|1ABM]], [[1lus|1LUS]], [[1luw|1LUW]]
</table>
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1luv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1luv OCA], [http://www.ebi.ac.uk/pdbsum/1luv PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1luv RCSB]</span>
== Disease ==
}}
[https://www.uniprot.org/uniprot/SODM_HUMAN SODM_HUMAN] Genetic variation in SOD2 is associated with susceptibility to microvascular complications of diabetes type 6 (MVCD6) [MIM:[https://omim.org/entry/612634 612634]. These are pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis.
== Function ==
[https://www.uniprot.org/uniprot/SODM_HUMAN SODM_HUMAN] Destroys superoxide anion radicals which are normally produced within the cells and which are toxic to biological systems.<ref>PMID:10334867</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lu/1luv_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1luv ConSurf].
<div style="clear:both"></div>


'''CATALYTIC AND STRUCTURAL EFFECTS OF AMINO-ACID SUBSTITUTION AT HIS 30 IN HUMAN MANGANESE SUPEROXIDE DISMUTASE: INSERTION OF VAL CGAMMA INTO THE SUBSTRATE ACCESS CHANNEL'''
==See Also==
 
*[[Superoxide dismutase 3D structures|Superoxide dismutase 3D structures]]
 
== References ==
==Overview==
<references/>
Catalysis of the disproportionation of superoxide by human manganese superoxide dismutase (MnSOD) is characterized by an initial burst of catalysis followed by a much slower region that is zero order in superoxide and due to a product inhibition by peroxide anion. We have prepared site-specific mutants with replacements at His30, the side chain of which lies along the substrate access channel and is about 5.8 A from the metal. Using pulse radiolysis to generate superoxide, we have determined that kcat/K(m) was decreased and product inhibition increased for H30V MnSOD, both by 1-2 orders of magnitude, compared with wild type, H30N, and H30Q MnSOD. These effects are not attributed to the redox potentials, which are similar for all of these variants. An investigation of the crystal structure of H30V Mn(III)SOD compared with wild type, H30Q, and H30N Mn(III)SOD showed the positions of two gamma carbons of Val30 in the active site; Cgamma1 overlaps Cgamma of His30 in wild type, and Cgamma2 extends into the substrate access channel and occupies the approximate position of a water molecule in the wild type. The data suggest that Cgamma2 of the Val side chain has significantly interrupted catalysis by this overlap into the access channel with possible overlap with the substrate-product binding site. This is supported by comparison of the crystal structure of H30V MnSOD with that of azide bound to Mn(III)SOD from Thermus thermophilus and by visible absorption spectra showing that azide binding to the metal in H30V Mn(III)SOD is abolished. Moreover, the presence of Val30 caused a 100-fold decrease in the rate constant for dissociation of the product-inhibited complex compared with wild type.
__TOC__
 
</StructureSection>
==About this Structure==
1LUV is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LUV OCA].
 
==Reference==
Catalytic and structural effects of amino acid substitution at histidine 30 in human manganese superoxide dismutase: insertion of valine C gamma into the substrate access channel., Hearn AS, Stroupe ME, Cabelli DE, Ramilo CA, Luba JP, Tainer JA, Nick HS, Silverman DN, Biochemistry. 2003 Mar 18;42(10):2781-9. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12627943 12627943]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Superoxide dismutase]]
[[Category: Cabelli DE]]
[[Category: Cabelli, D E.]]
[[Category: Hearn AS]]
[[Category: Hearn, A S.]]
[[Category: Luba JP]]
[[Category: Luba, J P.]]
[[Category: Ramilo CA]]
[[Category: Ramilo, C A.]]
[[Category: Silverman DN]]
[[Category: Silverman, D N.]]
[[Category: Stroupe ME]]
[[Category: Stroupe, M E.]]
[[Category: Tainer JA]]
[[Category: Tainer, J A.]]
[[Category: high resolution]]
[[Category: human manganese superoxide dismutase]]
[[Category: mn]]
[[Category: mnsod]]
[[Category: wild type]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:07:40 2008''

Latest revision as of 10:36, 14 February 2024

CATALYTIC AND STRUCTURAL EFFECTS OF AMINO-ACID SUBSTITUTION AT HIS 30 IN HUMAN MANGANESE SUPEROXIDE DISMUTASE: INSERTION OF VAL CGAMMA INTO THE SUBSTRATE ACCESS CHANNELCATALYTIC AND STRUCTURAL EFFECTS OF AMINO-ACID SUBSTITUTION AT HIS 30 IN HUMAN MANGANESE SUPEROXIDE DISMUTASE: INSERTION OF VAL CGAMMA INTO THE SUBSTRATE ACCESS CHANNEL

Structural highlights

1luv is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.85Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

SODM_HUMAN Genetic variation in SOD2 is associated with susceptibility to microvascular complications of diabetes type 6 (MVCD6) [MIM:612634. These are pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis.

Function

SODM_HUMAN Destroys superoxide anion radicals which are normally produced within the cells and which are toxic to biological systems.[1]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

References

  1. MacMillan-Crow LA, Thompson JA. Tyrosine modifications and inactivation of active site manganese superoxide dismutase mutant (Y34F) by peroxynitrite. Arch Biochem Biophys. 1999 Jun 1;366(1):82-8. PMID:10334867 doi:S0003-9861(99)91202-X

1luv, resolution 1.85Å

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